This invention relates to 24-homo vitamin D derivatives of formula I ##STR2## in which R.sup.1 means a hydrogen atom, a hydroxy or an acyloxy group with 1 to 8 carbon atoms,
R.sup.2 and R.sup.3, independently of one another, mean a linear or branched alkyl group exhibiting 1 to 4 carbon atoms, a trifluoromethyl group or together mean a saturated carbocyclic ring with 3 to 9 carbon atoms formed with carbon atom 25, PA1 R.sup.4 and R.sup.5, independently of one another mean a hydrogen atom or acyl group exhibiting 1 to 8 carbon atoms, and PA1 A and B each mean a hydrogen or together a second bond, PA1 n stands for 1, 2, 3, 4, or 5, PA1 as well as a process for their production, pharmaceutical preparations, which contain these compounds as well as their use for the production of pharmaceutical agents. PA1 R.sup.1 stands for a hydroxy group or PA1 R.sup.2 and R.sup.3 stand for a methyl group or PA1 R.sup.4 and R.sup.5 stand for a hydrogen atom and PA1 (5Z,7E,22E)-(1S,3R,24R)-9,10-seco-24a-homo-5,7,10(19),22-cholestatetraene-1 ,3,24-triol and PA1 (5Z,7E,22E)-(1S,3R,24S)-9,10-seco-24a-homo-5,7,10(19),22-cholestatetraene-1 ,3,24-triol. Natural vitamins D.sub.2 and D.sub.3 or their biologically active metabolites (natural vitamins D.sub.2 and D.sub.3 are biologically inactive in themselves and become active only after hydroxylation in the 25-position in the liver or in the 1-position in the kidney) exhibit as a characteristic feature a double bond between the positions C.sub.10 and C.sub.19, which is considered decisive for vitamin D activity (cf. general formula V). The action of Vitamins D.sub.2 and D.sub.3 consists of the stabilization of the plasma Ca.sup.++ and plasma phosphate levels; vitamins D.sub.2 and D.sub.3 counteract the reduction of plasma Ca.sup.++ levels. ##STR3## Ergocalciferol: R.sup..alpha. .dbd.R.sup.b .dbd.H, R.sup.c .dbd.CH.sub.3. Vitamin D.sub.2 PA1 Cholecalciferol:R.sup..alpha. .dbd.R.sup.b .dbd.R.sup.c .dbd.H Vitamin D.sub.3 PA1 25-Hydroxycholecalciferol:R.sup..alpha. .dbd.R.sup.c .dbd.H, R.sup.b .dbd.OH PA1 I.alpha.-Hydroxycholecalciferol: R.sup..alpha. .dbd.OH, R.sup.b .dbd.R.sup.c .dbd.H PA1 I.alpha.,25-Dihydroxycholecalciferol: R.sup..alpha. .dbd.R.sup.b .dbd.OH, R.sup.c .dbd.H Calcitriol PA1 B) (5Z,7E,22E)-(1S,3R,24S)-9,10-seco-homo-24a-5,7,10(19),22-cholestatetraene- 1,3,24-triol has a CF value of 0.8. PA1 Keratinocytes of newly born mice, with a slight change of the method of Yuspa, S. and Harris, C. C., "Altered differentiation of mouse epidermal cells treated with retinyl acetate in vitro," Exp. Cell Res. 86:95-105, 1974, are prepared and cultivated. PA1 Compound A=6.0.times.10.sup.-9 mol/l PA1 Compound B=9.5.times.10.sup.-9 mol/l PA1 R.sup.4' means a hydroxy protecting group and PA1 R.sup.2 and R.sup.3 as well as n have the meaning indicated in formula I. PA1 A and B either together mean a second bond or each means a hydrogen atom.
The acyloxy or acyl groups possible for the radicals R.sup.1, R.sup.4 and R.sup.5 are especially derived from saturated carboxylic acids or also from benzoic acid.
If R.sup.2 and R.sup.3 form a saturated carbocyclic ring together with carbon atom 25, the cyclopropyl, cyclopentyl, or cyclohexyl rings are especially preferred.
Preferred according to this invention are 24-homo vitamin D derivatives of general formula I in which:
n is 1, 2 or 3.
A double bond is preferably between carbon atoms 22 and 23.
Especially preferred are the compounds
double bond C 22/23
Besides their marked action on the calcium and phosphate metabolism, vitamin D.sub.2 and D.sub.3 and its derivatives also have proliferation-inhibiting and cell-differentiating actions (H. F. De Luca, The Metabolism and Function of Vitamin D in Biochemistry of Steroid Hormones, editor H. [two letters illegible] Makin, 2nd Edition, Blackwell Scientific Publications 1984, pp. 71-116). But overdose phenomena (hypercalcemia) can occur with vitamin D use.
1alpha-Cholecalciferols, hydroxylated in the 24 position, as produced from DE AS 25 26 981 have a lower toxicity than the corresponding unhydroxylated 1alpha-cholecalciferol. The hydroxylated compounds show a selective activation of the intestinal calcium absorption and a weaker bone absorption action than 1alpha-cholecalciferol.
The 24-hydroxy vitamin D analogues, described in international patent application WO 87/00834 can be used for treatment of disorders in humans and animals caused by abnormal cell proliferation and/or cell differentiation.
Quite recently a dissociation relative to the properties of bone absorption action and HL 60 cell differentiation was mentioned by De Luca for different 1,25-dihydroxy-homo vitamin D derivatives. The bone absorption action in vitro is in this case a direct measurement for the calcium mobilization in vivo.